It has been found that cultured neuroblastoma and teratoma cells co-aggregate with cerebellar cells from postnatal mice. Cerebellar cells aggregated by themselves differentiate in vivo both morphologically and biochemically. We have studied the transition from embryonic L-glycerol-3-phosphate dehydrogenase (alpha-GPDH) isozyme to the adult-type expression in these cerebellar aggregates and have found that if cerebellar cells are co-aggregated with tumor cells then isozyme transition is inhibited. The cerebellar cells continue to synthesize embryonic isozyme rather than switch to adult isozyme expression. Several types of experimentation suggest that cell-to-cell interaction, possibly mediated through the plasma membrane or cell surface, is involved in the repression of the adult-type isozyme. We propose to investigate the mechanism by which this repression occurs by analyzing cerebellar cell aggregates that have been co-aggregated with disrupted cell preparations and purified subcellular fractions. If a subcellular fraction is identified then further experimentation will involve isolation and identification of the chemical structures involved in these interactions. Other experiments will include immunofluorescence and ultrastructural analysis of co-aggregated cultures in order to assess whether there is a failure of cell sorting or cell-to-cell contact in the aggregates.